Genetic Variant GDF7:c.*6968T>C (chr2-20678393-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182828.4(GDF7):c.*6968T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,270 control chromosomes in the GnomAD database, including 8,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 8046 hom., cov: 34)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

GDF7
NM_182828.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

21 publications found

Variant links:

Genes affected

GDF7 (HGNC:4222): (growth differentiation factor 7) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein may play a role in the differentiation of tendon cells and spinal cord interneurons. A mutation in this gene may be associated with increased risk for Barrett's esophagus and esophageal adenocarcinoma. [provided by RefSeq, Sep 2016]

GDF7 links:

ENSG00000270100 (HGNC:):

ENSG00000270100 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF7	NM_182828.4	MANE Select	c.*6968T>C		3_prime_UTR	Exon 2 of 2	NP_878248.2	Q7Z4P5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF7	ENST00000272224.5	TSL:1 MANE Select	c.*6968T>C		3_prime_UTR	Exon 2 of 2	ENSP00000272224.3	Q7Z4P5
	ENSG00000270100	ENST00000602445.1	TSL:6	n.540A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45629

AN:

152150

Hom.:

8039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.300

AC:

45633

AN:

152266

Hom.:

8046

Cov.:

AF XY:

0.303

AC XY:

22549

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.108

AC:

4481

AN:

41572

American (AMR)

AF:

0.346

AC:

5295

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1371

AN:

3470

East Asian (EAS)

AF:

0.472

AC:

2445

AN:

5182

South Asian (SAS)

AF:

0.369

AC:

1779

AN:

4826

European-Finnish (FIN)

AF:

0.362

AC:

3835

AN:

10594

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25188

AN:

68004

Other (OTH)

AF:

0.357

AC:

755

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.354

Hom.:

4311

Bravo

AF:

0.286

Asia WGS

AF:

0.417

AC:

1451

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.8

(source)

DANN

Benign

0.80

PhyloP100

-0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over